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Biomedical subjects

H Larsson

Publications and source records attributed to H Larsson.

At least 91 records · Page 5Linked to original sources

Local acid production and Helicobacter pylori: a unifying hypothesis of gastroduodenal disease.

We aimed to produce a unifying hypothesis to explain the different locations of peptic ulcer and gastritis observed in different populations. The pre-Helicobacter pylori literature on patterns of gastroduodenal disease was reviewed and compared with recent human and animal findings on H. pylori infection. Early observations revealed that duodenal and non-pre-pyloric ulcers tend to be mutually exclusive. In duodenal ulcer patients, gastritis is usually restricted to the antrum, while gastric ulcer patients experience more severe pangastritis. The manipulation of acid output by surgery or acid suppressive therapy alters the distribution of gastritis. Recent experimental evidence in humans and animals has shown that these changes parallel changes in the distribution and cellular responses to H. pylori infection. We propose that the most important factor in the ecology of the H. pylori-infected stomach is local acid production. Local acid production determines the location and severity of inflammation and the clinical outcome of this bacterial infection. Priority research areas should be the investigation of the in vivo behaviour of H. pylori in the acid and the non-acid producing areas of the stomach and the measurement of acid output in populations known to have different patterns of gastroduodenal disease.

Animals↗

Conventional and controlled release diltiazem. Bioavailability in healthy volunteers and anti-anginal effects in combination with metoprolol in stable angina pectoris.

Diltiazem CR tablets 120 mg b.i.d. for 1 week were compared with plain tablets 60 mg q.i.d. in 13 healthy male volunteers in a study of pharmacokinetic variables. Their antianginal efficacy was also compared in 23 patients with stable angina pectoris who were already on metoprolol. Both studies were of randomised, cross over design, and the clinical study was double blind. The pharmacokinetic variables of the two formulations were very similar except for the longer tmax of 4.4 h for diltiazem CR in comparison to 2.9 h for the plain tablets. The mean relative bioavailability of diltiazem CR in comparison with plain tablets was 1.14. The clinical study showed that after four weeks on diltiazem CR 120 mg b.i.d. or diltiazem plain tablets 60 mg q.i.d. in addition to metoprolol, there were significant decreases in weekly anginal attacks from 11 to 5 attacks/week, the number of nitroglycerin tablets consumed from 6 to 3 tablets/week, and an increase in the maximum workload from 116 to 126 and 123 W for diltiazem CR and plain diltiazem tablets, respectively, as compared to placebo. Five of the patients were angina free during diltiazem treatment. No difference in anti-anginal efficacy between the two preparations was seen. It was concluded that CR 120 mg b.i.d. appears bioequivalent to plain diltiazem tablets 60 mg q.i.d.

Adult↗

Changed blood rheology in patients with idiopathic dilated cardiomyopathy.

Rheologic properties of blood were studied in 8 patients with dilated cardiomyopathy (DCM) and in 10 healthy subjects. Whole-blood viscosity was measured at four different shear rates, by means of a computer-controlled rotational viscometer. The patients had significantly higher blood viscosity at all shear rates, both at their natural hematocrits and after an in vitro adjustment of sample hematocrits to 45%. Erythrocyte filterability (5 microns pore size) was significantly lower, fibrinogen concentration significantly higher, and HDL-cholesterol concentration significantly lower in the patient group. No significant differences were found regarding hematocrit, mean corpuscular volume, hemoglobin concentration, leukocyte count and filterability (8 microns pore size), plasma viscosity, and total cholesterol concentration. The measured hemorheologic abnormalities may contribute to the previously reported reduction of coronary blood flow reserve in DCM patients and to myocardial microcirculatory disturbances, which have been suggested as a cause for DCM.

Adult↗

Characterization of the 97 and 103 kDa forms of starch branching enzyme from potato tubers.

N-Terminal analysis, peptide mapping and partial peptide sequencing of the 97 and 103 kDa forms of starch branching enzyme from potato tubers showed that the two forms are highly related. A comparison with sequence data in the literature showed that these forms belong to the starch branching enzyme isoform I family. An internal cDNA fragment was obtained using PCR technology on potato tuber RNA with two oligonucleotide primers constructed from the peptide sequence data. Southern blot analysis using the PCR fragment as probe showed that there is only one gene locus encoding this isoform of the enzyme in Solanum tuberosum as well as in Solanum commersonii.

1,4-alpha-Glucan Branching Enzyme↗

Breath-by-breath determination of inspiratory occlusion pressure.

In order to determine the influence of breath-by-breath measurement of inspiratory occlusion pressure (P0.1) on the pulmonary ventilation, the respiratory timing and the central inspiratory activity as reflected by P0.1 per se, nine healthy males were studied as they breathed in a valve assembly including an externally controlled occlusion valve. A new technique was used, terminating occlusions at a preset inspiratory threshold pressure and determining P0.1 from linear regression of the mouth pressure curve. Subjects were studied at rest and during light exercise, with the occluding function (threshold pressure) on or off during alternating periods. Breath-by-breath variability of P0.1 was of the order of 30%. We found no detectable influence of breath-by-breath short-lasting inspiratory occlusions on tidal volume and ventilation. However, mean inspiratory flow was slightly increased due to a shortened inspiratory duration at rest and during light exercise. Also, raising the threshold pressure for occlusions from 69 to 147 Pa (0.7 to 1.5 cm H2O) resulted in a 20% increase of P0.1. We conclude that breath-by-breath measurement of P0.1 is a feasible technique, and that the slightly shortened inspiratory duration and the increased P0.1 with increased threshold pressure may not necessarily be expressions of a true stimulation of the central inspiratory activity.

Adult↗

Effects of chloride transport inhibitors on intestinal fluid and ion transport in vivo and in vitro.

The hypothesis that intestinal fluid secretion is driven by Cl- has been tested by investigating the effects of NPPB (5-nitro-2-(3-phenyl-propylamino)-benzoate), a blocker of Cl- channels in nephrons, and the loop diuretic bumetanide, an inhibitor of the Na+, K+, 2Cl(-)-co-transporter. Both NPPB (IC50 (inhibitory concentration) approximately 100 microM) and bumetanide (IC50 approximately 2 microM) inhibited stimulated short-circuit current (Isc) in monolayers of a colonic cell line T84. NPPB also inhibited 36Cl- uptake by these cells, indicating that NPPB acts as a Cl- channel blocker in the T84 cells. NPPB (300 microM) and bumetanide (10 microM) abolished both stimulated Isc and Cl- secretion in isolated rat colonic mucosa. As judged by autoradiography, [3H]NPPB was found both in the crypts and at the surface after exposure of either side to the compound. In line with these results, NPPB and bumetanide reduced stimulated fluid secretion in everted colon sacs from the rat. In the anaesthetized rat model, neither bumetanide nor NPPB affected the net fluid transport. After luminal administration of [3H]NPPB to the rat, radioactivity was found mainly in the villus tips, whereas no labelling was found in the crypts. NPPB was bound to plasma protein (99%), and the inhibitory effects of both NPPB and bumetanide on Isc in T84 cells and fluid secretion in the colonic sacs decreased in the presence of albumin, again indicating that the compounds might not reach the in vivo target, or that the mechanism for fluid secretion in vivo may not be explained solely by the secretion of Cl-.

Animals↗

Blood viscosity during long-term treatment with ticlopidine in patients with intermittent claudication. A double-blind study.

The aim was to test within a randomized, double-blind trial whether the antiaggregant drug ticlopidine might reduce blood viscosity as has been claimed. Sixteen patients with intermittent claudication were studied before and after three years of treatment with ticlopidine, 500 mg/day, or placebo. At baseline, the viscosity values were significantly higher as compared with a reference group of healthy subjects. Whole-blood viscosity, measured at four different shear rates at hematocrit adjusted to a standard 40%, decreased significantly at follow-up, with no difference between ticlopidine treatment and placebo. Hematocrit showed a slight increase in the placebo group. The viscosity parameters were unrelated to lower limb blood flow variables, ankle/brachial index, and walking distances. The mechanism behind the overall decrease in whole-blood viscosity is obscure but could possibly be explained by lifestyle changes. Smoking habits were, however, unaltered. Since plasma viscosity remained increased, it might indicate that some erythrocyte factor, notably red cell aggregability and deformability, had improved. It is concluded that ticlopidine had no long-term effect on blood viscosity.

Aged↗

Development of nocturnal respiratory disturbance in untreated patients with obstructive sleep apnea syndrome.

Patient histories suggest that obstructive sleep apnea syndrome (OSAS) is a progressive condition. To investigate whether this could be shown in data from sleep recordings, 42 patients with OSAS were retrospectively studied. All had undergone a screening recording of respiration movements and oximetry at least 6 months (average, 16 months) prior to a diagnostic polysomnogram including these parameters. No treatment was given in the meantime. In the first recording, mean oxygen desaturation index (ODI, average number of desaturations of > 4 percent per sleeping hour) was 10; periodic, obstructive respiration movements occurred during (average) 36 percent of total estimated sleeping time, and mean nadir SaO2 was 85 percent. In the second recording, mean ODI was 21 (significant change, p = 0.0002), periodic respiration time was 61 percent, and nadir SaO2 was 80 percent (p = 0.0001, respectively). In 26 of 42 patients (62 percent), ODI had increased by > 50 percent. Increases in ODIs and periodic breathing were significantly correlated to increases in body weight. There were, however, exceptional patients with considerable increases in respiratory disturbance despite weight loss. The greatest changes were found in the patients who had the highest apnea indices in the polysomnograms. Early treatment may therefore be justified, since a borderline case may change to severe OSAS in 1 to 2 years' time. Follow-up recordings of untreated patients are important.

Aged↗

Prevention of serious cardiac events by low-dose aspirin in patients with silent myocardial ischaemia. The Research Group on Instability in Coronary Artery Disease in Southeast Sweden.

On exercise testing after an episode of unstable coronary artery disease (CAD; unstable angina or non-Q-wave myocardial infarction), a proportion of patients show ST-segment depression, indicating myocardial ischaemia, but do not report concomitant symptoms of angina. Treatment of such "silent" ischaemia aims mainly to reduce the risk of subsequent cardiac events. We have studied the effect of low-dose aspirin in patients with myocardial ischaemia defined at the predischarge test as silent (though patients might have had symptomatic ischaemia at other times) or symptomatic. 740 men with unstable CAD aged 70 years or less underwent symptom-limited exercise testing before hospital discharge; 144 showed ST depression without pain and 230 ST depression with simultaneous chest pain. Of the silent ischaemia group, 67 were randomly assigned placebo and 77 aspirin (75 mg daily); the corresponding numbers in the symptomatic group were 125 and 105. Angina symptoms were less common in the silent than in the symptomatic ischaemia group both before inclusion and during follow-up, and a greater proportion of the silent ischaemia group were included because of myocardial infarction. In both ischaemia groups aspirin treatment reduced the risk of subsequent myocardial infarction or death by 3 months' follow-up (silent 4% of aspirin-treated vs 21% of placebo-treated patients, p = 0.004; symptomatic 9% vs 18%, p = 0.05); at 12 months' follow-up a significant benefit of aspirin was still apparent in the silent ischaemia group (9% vs 28%, p = 0.005) but not in the symptomatic group (13% vs 22%, p = 0.109). Low-dose aspirin reduced the risk of subsequent myocardial infarction at least as well in silent as in symptomatic myocardial ischaemia. Since improvement of outlook is the main treatment objective in symptom-free patients, aspirin should be a mainstay of their treatment.

Aged↗

The predictive value of silent ischemia at an exercise test before discharge after an episode of unstable coronary artery disease. RISC Study Group.

The prognostic value of silent ischemia during a symptom-limited predischarge exercise test (ET) was evaluated in 740 men after an episode of unstable angina or non-Q wave myocardial infarction. The 51% of patients with ST depression at the ET had a higher rate of myocardial infarction or death after 1 year (18%) compared with those without ST depression (9%; p less than 0.01). This increased risk was not influenced by the presence or absence of pain at the ET: 18.3% in patients with painful ischemia compared with 18.1% in patients with silent ischemia. However, ST depression combined with pain at the ET predicted a higher incidence of class III or IV angina at follow-up (43.9% compared with 16.7% in the group with asymptomatic ST depression; p less than 0.001). Because revascularization in addition to alleviating symptoms also enhances the prognosis in certain groups of patients, selections for coronary angiography and possible revascularization should not be made only on the basis of symptoms but also on the presence of myocardial ischemia, whether symptomatic or not.

Coronary Disease↗

Diagnostic and prognostic importance of ST recording after an episode of unstable angina or non-Q-wave myocardial infarction.

The diagnostic and prognostic value of ST recordings in unstable coronary artery disease were evaluated in 198 men below 70 years of age admitted to the coronary care unit because of chest pain due to myocardial ischaemia but without the development of Q-wave infarction. The ST recordings were performed for 24 h in bed in the CCU (n = 75) between 6 and 66 hours after the last episode of pain, before discharge during ambulation in hospital 4-6 days after admission (n = 198), and ambulatory out of hospital 1 month later (n = 109). The long-term ECG was registered from bipolar leads corresponding to V2 and V5 using two-channel FM-recorders. Significant ST episodes were defined as ST segment deviation greater than or equal to 0.1 mV from baseline and lasting for at least 1 min. During the recordings 85-90% of the patients were treated with betablockers and 27-41% also with calcium channel blockers. In the CCU recordings, ST depression occurred in 23% of the patients, 21% had asymptomatic and 7% symptomatic episodes. Before discharge the ST recordings showed ST depression in 18% of the patients, 16% asymptomatic and 7% symptomatic. Ambulatory monitoring after 1 month showed a higher occurrence of ST depressions--33% (P less than 0.01 compared to day 5), 26% had episodes without pain and 13% painful episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Neurogenic effects on the palatopharyngeal muscle in patients with obstructive sleep apnoea: a muscle biopsy study.

Muscle biopsies from the palatopharyngeal muscle of eight patients with obstructive sleep apnoea were performed during uvulopalatopharyngoplasty. Control biopsies were performed during tonsillectomy in seven control patients with no history of symptoms suggesting obstructive sleep apnoea. The diagnosis was based on the patient's history and a whole night recording of arterial oxygen saturation and respiration movements. The mean number of oxygen desaturations > or = 4% per sleeping hour was 39 (range 7-80) in patients with obstructive sleep apnoea. In the control patients the occurrence of muscle fibre type and size relation between type I and type II fibres were comparable to what is found in the quadriceps femoris muscle, but the mean size of the fibres was < 25% of what is found in limb muscles. All biopsies from patients with obstructive sleep apnoea showed abnormalities. Atrophy with a fascicular distribution, increased number of angulated atrophic fibres, a twin or multiple peak distribution of the fibre size spectra, and an abnormal distribution of fibre types in many muscle fascicles corresponding to "type grouping" all points to a neurogenic alteration. This neurogenic lesion may be a primary phenomenon or secondary to the trauma of repetitive and prolonged stretching of the pharyngeal structures during apnoeas. A disturbance of the function of the dilating muscles of the upper airway may be important in causing the abnormal airway collapse seen in obstructive sleep apnoea.

Adult↗

Temperature thresholds in the oropharynx of patients with obstructive sleep apnea syndrome.

The temperature thresholds for warmth and cold were determined on the oropharyngeal mucosa of 15 patients with obstructive sleep apnea syndrome (OSAS) and 15 age-matched nonsnoring control subjects. We found that six of the patients with OSAS were not able to detect either the upper (50 degrees C) or lower (25 degrees C) temperature limits of the test when recording from the tonsillar pillar, whereas all control subjects detected the temperature change within the measuring range. The OSAS patients showed a statistically significant higher threshold for warmth on the anterior tonsillar pillar, 46.8 degrees C (95% confidence interval 45.2-48.4) versus 42.5 degrees C (41.3-43.8) for the control subjects (p = 0.0006). The same was found on the tip of the tongue-40.1 degrees C (38.7-41.6) for OSAS patients and 38.2 degrees C (37.1-39.4) for the control subjects (p = 0.036). Determination of temperature thresholds on the skin is an established method of detecting a neuropathy. We speculate that patients with OSAS suffer from a neuropathy in the pharynx caused by prolonged and progressive trauma to the pharyngeal structures from vibration induced by snoring and/or stretching of the structures during apneas. A neuropathy may interfere with the normal stabilizing function of the pharyngeal muscles and with the local reflex mechanism preventing the upper airway from collapsing during inspiration. It is thus possible that snoring itself, by inducing a neuropathy in the pharynx, may contribute to the sequence of events that transform a snorer into a patient suffering from OSAS.

Adult↗

The diagnostic reliability of magnetically evoked motor potentials in multiple sclerosis.

In a prospective study, we evaluated the technique of magnetically evoked motor potentials (MEP) in the diagnosis of multiple sclerosis (MS). We consecutively included 68 patients with symptoms or signs compatible with a demyelinative CNS affection. We subjected all patients to CSF analysis, MRI studies of the brain and brainstem, visual evoked potentials (VEP), brainstem auditory evoked potentials (BAEP), and somatosensory evoked potentials (SSEP). We then used the results to categorize the patients according to the Poser criteria of multiple sclerosis. Blinded from the results of the above investigations, one of the authors made MEP recordings from three muscles in the upper limbs and two in the lower limbs in all 68 patients. Forty patients received an MS diagnosis, and in these, MRI was positive in 88%, MEP in 83%, VEP in 67%, SSEP in 63%, and BAEP in 42%. As to the diagnosis of MS, the reliability of a prolonged central motor conduction time (CMCT) was 0.83 (0.73 to 0.93), while the reliability of a normal CMCT was 0.75 (0.61 to 0.98). The information gained by MRI was best supplemented by VEP. Of the neurophysiologic tests, the MEP was in closest agreement with the MRI with a concordance of 85%.

Acoustic Stimulation↗

Potential differences in the inferior vena cava and between cava and extravascular electrode at leg contraction in man.

When a voluntary adult male contracted his leg muscles, electric potential differences were recorded between platinum electrodes positioned inside the vena cava or between the vena cava and the grounded skin. Two experiments confirm that potential differences at leg contractions in man have a similar appearance as those in the rat at pain-evoked contractions of leg muscles. Platinum electrodes were used in man. The potential differences obtained are thereafter compared with recordings with Ag-AgCl electrodes in salt-bridges in the rat. Slow potential waves with superimposed irregular potential oscillations are recorded in man as previously found in the rat using platinum or Ag-AgCl electrodes. The findings indicate that vascular-interstitial routes participate in a vascular-interstitial-neuromuscular closed circuit, which is activated at contraction of the muscles.

Adult↗

Reversed-phase liquid chromatographic method for the simultaneous determination of the antimalarial drugs sulfadoxine, pyrimethamine, mefloquine and its major carboxylic metabolite in plasma.

A high-performance liquid chromatographic (HPLC) method for the simultaneous determination of sulfadoxine, pyrimethamine, mefloquine and the carboxylic metabolite of mefloquine in plasma is described. After the proteins have been precipitated with a combination of zinc sulphate and acetonitrile containing two internal standards, pyrimethamine and mefloquine are extracted as bases and sulfadoxine and the carboxylic metabolite of mefloquine as ion-pairs with tetrabutylammonium. The drugs are separated by HPLC on a 3 micron octadecylsilica column with ultraviolet detection at 229 nm. The method is simple and reliable and enables the simultaneous determination of the drugs in 600-microliter plasma samples with a sensitivity suitable for standard drug monitoring purposes.

Antimalarials↗